Current Nutrition Reports

, Volume 3, Issue 3, pp 213–222 | Cite as

Genetic Modification of the Effects of Alcohol on Metabolic and Clinical Phenotypes: A Review

  • James N. Kiage
  • Laurence O. James
  • Edmond K. Kabagambe
Genetics (GVZ Dedoussis, Section Editor)


Moderate alcohol intake is associated with improved high-density lipoprotein cholesterol, inflammation, insulin sensitivity and a lower risk of cardiovascular disease. These beneficial effects have not been consistent across studies. Genetic mechanisms that regulate alcohol intake and metabolism may in part explain the inconsistencies. In this report we review evidence of the impact of genetic variation on the effects of moderate alcohol intake on metabolic and clinical phenotypes. We focused on single nucleotide polymorphisms in major alcohol-metabolizing enzyme genes, particularly alcohol dehydrogenases (i.e., ADH1B, ADH1C and ADH7), aldehyde dehydrogenase, and cytochrome P450 2E1 because of their reported effects on gene transcription rates, enzyme activity and association with clinical endpoints. We report that while there is evidence for genetic modification of the effects of alcohol on various metabolic phenotypes, most studies are based on minimally genotyped populations. Studies using dense markers (e.g., from exome sequencing) are needed and may explain some of the inconsistencies.


Alcohol Genetic modification Metabolic Lipids Inflammation Diabetes Cardiovascular disease Alcohol metabolizing enzymes Alcohol dehydrogenases CYP2E1 ALDH2 Nutrition 



Alcohol dehydrogenase


Aldehyde dehydrogenase 2


Apolipoprotein C 3


Cardiovascular disease


C-reactive protein


High-density lipoprotein cholesterol


Soluble intercellular adhesion molecule-1




Lipoprotein lipase


Low-density lipoprotein cholesterol


Microsomal ethanol oxidizing system




Proprotein convertase subtilisin/kexin type 9


Plasminogen activator inhibitor-1


Single nucleotide polymorphisms


Soluble vascular cell adhesion molecule-1


Tissue plasminogen activator


Tumor necrosis factor

and WBC

White blood cell count



Edmond K. Kabagambe was supported by the National Scientist Development Grant # 0635323N from the American Heart Association.

Compliance with Ethics Guidelines

Conflict of Interest

James N. Kiage, Laurence O. James, and Edmond K. Kabagambe declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Zaridze D, Lewington S, Boroda A, Scelo G, Karpov R, Lazarev A, et al. Alcohol and mortality in Russia: prospective observational study of 151,000 adults. Lancet. 2014;383(9927):1465–73. doi:10.1016/S0140-6736(13)62247-3S0140-6736(13)62247-3.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med. 2006;166(22):2437–45. doi:10.1001/archinte.166.22.2437.PubMedCrossRefGoogle Scholar
  3. 3.
    Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. BMJ. 1996;312(7033):731–6.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Rimm E. Alcohol and cardiovascular disease. Curr Atheroscler Rep. 2000;2(6):529–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Mukamal KJ, Conigrave KM, Mittleman MA, Camargo Jr CA, Stampfer MJ, Willett WC, et al. Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Engl J Med. 2003;348(2):109–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Tanasescu M, Hu FB, Willett WC, Stampfer MJ, Rimm EB. Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus. J Am Coll Cardiol. 2001;38(7):1836–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Schroder H, Ferrandez O, Jimenez Conde J, Sanchez-Font A, Marrugat J. Cardiovascular risk profile and type of alcohol beverage consumption: a population-based study. Ann Nutr Metab. 2005;49(2):100–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Mukamal KJ, Rimm EB. Alcohol's effects on the risk for coronary heart disease. Alcohol Res Health. 2001;25(4):255–61.PubMedGoogle Scholar
  10. 10.
    Hines LM, Stampfer MJ, Ma J, Gaziano JM, Ridker PM, Hankinson SE, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med. 2001;344(8):549–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Mukamal KJ, Cushman M, Mittleman MA, Tracy RP, Siscovick DS. Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study. Atherosclerosis. 2004;173(1):79–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Mukamal KJ, Jadhav PP, D'Agostino RB, Massaro JM, Mittleman MA, Lipinska I, et al. Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort. Circulation. 2001;104(12):1367–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Renaud SC, Ruf JC. Effects of alcohol on platelet functions. Clin Chim Acta. 1996;246(1–2):77–89.PubMedCrossRefGoogle Scholar
  14. 14.
    Ruf JC. Alcohol, wine and platelet function. Biol Res. 2004;37(2):209–15.PubMedCrossRefGoogle Scholar
  15. 15.
    Albert MA, Glynn RJ, Ridker PM. Alcohol consumption and plasma concentration of C-reactive protein. Circulation. 2003;107(3):443–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Davies MJ, Baer DJ, Judd JT, Brown ED, Campbell WS, Taylor PR. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial. JAMA. 2002;287(19):2559–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med. 1996;125(5):384–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Vogel RA. Alcohol, heart disease, and mortality: a review. Rev Cardiovasc Med. 2002;3(1):7–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Burns J, Crozier A, Lean ME. Alcohol consumption and mortality: is wine different from other alcoholic beverages? Nutr Metab Cardiovasc Dis. 2001;11(4):249–58.PubMedGoogle Scholar
  20. 20.
    Fuchs FD, Chambless LE, Folsom AR, Eigenbrodt ML, Duncan BB, Gilbert A, et al. Association between alcoholic beverage consumption and incidence of coronary heart disease in whites and blacks: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 2004;160(5):466–74.PubMedCrossRefGoogle Scholar
  21. 21.
    Sempos CT, Rehm J, Wu T, Crespo CJ, Trevisan M. Average volume of alcohol consumption and all-cause mortality in African Americans: the NHEFS cohort. Alcohol Clin Exp Res. 2003;27(1):88–92. doi:10.1097/01.ALC.0000046597.92232.73.PubMedCrossRefGoogle Scholar
  22. 22.
    Goldberg IJ. To drink or not to drink? N Engl J Med. 2003;348(2):163–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Goldberg IJ, Mosca L, Piano MR, Fisher EA. AHA Science Advisory. Wine and your heart: a science advisory for healthcare professionals from the Nutrition Committee, Council on Epidemiology and Prevention, and Council on Cardiovascular Nursing of the American Heart Association. Stroke. 2001;32(2):591–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Ruf JC. Wine and polyphenols related to platelet aggregation and atherothrombosis. Drugs Exp Clin Res. 1999;25(2–3):125–31.PubMedGoogle Scholar
  25. 25.
    Kabagambe EK, Baylin A, Ruiz-Narvarez E, Rimm EB, Campos H. Alcohol intake, drinking patterns and risk of nonfatal acute myocardial infarction in Costa Rica. Am J Clin Nutr. 2005;82(2):1336–45.PubMedGoogle Scholar
  26. 26.
    Klatsky AL, Friedman GD, Armstrong MA, Kipp H. Wine, liquor, beer, and mortality. Am J Epidemiol. 2003;158(6):585–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Judd SE, McClure LA, Howard VJ, Lackland DT, Halanych JH, Kabagambe EK. Heavy drinking is associated with poor blood pressure control in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Int J Environ Res Pub Health. 2011;8(5):1601–12. doi:10.3390/ijerph8051601ijerph-08-01601.CrossRefGoogle Scholar
  28. 28.
    Fuchs FD, Chambless LE, Whelton PK, Nieto FJ, Heiss G. Alcohol consumption and the incidence of hypertension: the atherosclerosis risk in communities study. Hypertension. 2001;37(5):1242–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ. Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics. 1988;2(3):209–14.PubMedCrossRefGoogle Scholar
  30. 30.
    Bosron WF, Lumeng L, Li TK. Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. Mol Aspects Med. 1988;10(2):147–58.PubMedCrossRefGoogle Scholar
  31. 31.
    Konishi T, Calvillo M, Leng AS, Feng J, Lee T, Lee H, et al. The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men. Exp Mol Pathol. 2003;74(2):183–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Konishi T, Smith JL, Lin KM, Wan YJ. Influence of genetic admixture on polymorphisms of alcohol-metabolizing enzymes: analyses of mutations on the CYP2E1, ADH2, ADH3 and ALDH2 genes in a Mexican-American population living in the Los Angeles area. Alcohol Alcohol. 2003;38(1):93–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Wan YJ, Poland RE, Lin KM. Genetic polymorphism of CYP2E1, ADH2, and ALDH2 in Mexican-Americans. Genet Test. 1998;2(1):79–83.PubMedCrossRefGoogle Scholar
  34. 34.
    Kidd KK. ALFRED database. 2014.
  35. 35.
    Suzuki Y, Ando F, Ohsawa I, Shimokata H, Ohta S. Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese. J Hum Genet. 2006;51(1):31–7. doi:10.1007/s10038-005-0318-9.PubMedCrossRefGoogle Scholar
  36. 36.
    Aung LH, Yin RX, Wu DF, Cao XL, Hu XJ, Miao L. Proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism interacts with alcohol consumption to modulate serum lipid levels. Int J Med Sci. 2013;10(2):124–32. doi:10.7150/ijms.5296ijmsv10p0124.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.•
    Baik I, Lee S, Kim SH, Shin C. A lipoprotein lipase gene polymorphism interacts with consumption of alcohol and unsaturated fat to modulate serum HDL-cholesterol concentrations. J Nutr. 2013;143(10):1618–25. doi:10.3945/jn.113.175315jn.113.175315. This article provides unique evidence on the effect of the LPL gene on alcohol-related phenotypes.
  38. 38.•
    Yin RX, Li YY, Wu JZ, Pan SL, Liu CW, Lin WX, et al. Interactions between the apolipoprotein a1/c3/a5 haplotypes and alcohol consumption on serum lipid levels. Alcohol Clin Exp Res. 2013;37(2):234–43. doi:10.1111/j.1530-0277.2012.01918.x. This article provides new evidence on the role of the ApoC3 gene in modifying the effects of alcohol on metabolic phenotypes.PubMedCrossRefGoogle Scholar
  39. 39.
    Corbex M, Poirier O, Fumeron F, Betoulle D, Evans A, Ruidavets JB, et al. Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction. Genet Epidemiol. 2000;19(1):64–80. doi:10.1002/1098-2272(200007)19:1<64::AID-GEPI5>3.0.CO;2-E.PubMedCrossRefGoogle Scholar
  40. 40.
    Lieber CS. Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health. 2003;27(3):220–31.PubMedGoogle Scholar
  41. 41.
    Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol. 2004;34(1):9–19.PubMedCrossRefGoogle Scholar
  42. 42.
    Anon. Medical students' handbook: alcohol and health. 3rd ed. London: The Medical council on alcohol; 2003.Google Scholar
  43. 43.
    Osier M, Pakstis AJ, Kidd JR, Lee JF, Yin SJ, Ko HC, et al. Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. Am J Hum Genet. 1999;64(4):1147–57.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Gemma S, Vichi S, Testai E. Individual susceptibility and alcohol effects: biochemical and genetic aspects. Ann Ist Super Sanita. 2006;42(1):8–16.PubMedGoogle Scholar
  45. 45.
    Baraona E, Abittan CS, Dohmen K, Moretti M, Pozzato G, Chayes ZW, et al. Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res. 2001;25(4):502–7. doi:10.1111/j.1530-0277.2001.tb02242.x.PubMedCrossRefGoogle Scholar
  46. 46.
    Osier MV, Pakstis AJ, Soodyall H, Comas D, Goldman D, Odunsi A, et al. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am J Hum Genet. 2002;71(1):84–99.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Zuo L, Gelernter J, Kranzler HR, Stein MB, Zhang H, Wei F, et al. ADH1A variation predisposes to personality traits and substance dependence. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):376–86. doi:10.1002/ajmg.b.30990.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Kang G, Bae K-Y, Kim S-W, Kim J, Shin H-Y, Kim J-M, et al. Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism. Alcohol Clin Exp Res. 2014. doi:10.1111/acer.12427.Google Scholar
  49. 49.
    Osier MV, Lu RB, Pakstis AJ, Kidd JR, Huang SY, Kidd KK. Possible epistatic role of ADH7 in the protection against alcoholism. Am J Med Genet B Neuropsychiatr Genet. 2004;126(1):19–22.CrossRefGoogle Scholar
  50. 50.
    Tsutsumi M, Wang JS, Takase S, Takada A. Hepatic messenger RNA contents of cytochrome P4502E1 in patients with different P4502E1 genotypes. Alcohol Alcohol. 1994;29 Suppl 1:29–32.Google Scholar
  51. 51.
    Tsutsumi M, Takada A, Wang JS. Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease. Gastroenterology. 1994;107(5):1430–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Stephens EA, Taylor JA, Kaplan N, Yang CH, Hsieh LL, Lucier GW, et al. Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans. Eur Am Taiwan Pharmacogenet. 1994;4(4):185–92.CrossRefGoogle Scholar
  53. 53.
    Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004;351(25):2599–610.PubMedCrossRefGoogle Scholar
  54. 54.
    Goedde HW, Agarwal DP, Harada S. Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. Clin Genet. 1979;16(1):29–33.PubMedCrossRefGoogle Scholar
  55. 55.
    Oota H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SL, et al. The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination. Ann Hum Genet. 2004;68(Pt 2):93–109.PubMedCrossRefGoogle Scholar
  56. 56.
    Crabb DW, Edenberg HJ, Bosron WF, Li TK. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. J Clin Invest. 1989;83(1):314–6.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev. 2014;94(1):1–34. doi:10.1152/physrev.00017.201394/1/1.PubMedCrossRefGoogle Scholar
  58. 58.
    Goedde HW, Agarwal DP, Harada S, Rothhammer F, Whittaker JO, Lisker R. Aldehyde dehydrogenase polymorphism in North American, South American, and Mexican Indian populations. Am J Hum Genet. 1986;38(3):395–9.PubMedCentralPubMedGoogle Scholar
  59. 59.
    Freiberg MS, Cabral HJ, Heeren TC, Vasan RS, Curtis ER. Alcohol consumption and the prevalence of the Metabolic Syndrome in the US: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27(12):2954–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Tabengwa EM, Wheeler CG, Yancey DA, Grenett HE, Booyse FM. Alcohol-induced up-regulation of fibrinolytic activity and plasminogen activators in human monocytes. Alcohol Clin Exp Res. 2002;26(8):1121–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Brinton EA. Effects of ethanol intake on lipoproteins and atherosclerosis. Curr Opin Lipidol. 2010;21(4):346–51. doi:10.1097/MOL.0b013e32833c1f41.PubMedCrossRefGoogle Scholar
  62. 62.
    Shai I, Rimm EB, Schulze MB, Rifai N, Stampfer MJ, Hu FB. Moderate alcohol intake and markers of inflammation and endothelial dysfunction among diabetic men. Diabetologia. 2004;47(10):1760–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Sacanella E, Estruch R. The effect of alcohol consumption on endothelial adhesion molecule expression. Addict Biol. 2003;8(4):371–8. doi:10.1080/13556210310001656376MM731QTA7FXR6YBK.PubMedCrossRefGoogle Scholar
  64. 64.
    Volpato S, Pahor M, Ferrucci L, Simonsick EM, Guralnik JM, Kritchevsky SB, et al. Relationship of alcohol intake with inflammatory markers and plasminogen activator inhibitor-1 in well-functioning older adults: the Health, Aging, and Body Composition study. Circulation. 2004;109(5):607–12. doi:10.1161/01.CIR.0000109503.13955.00109/5/607.PubMedCrossRefGoogle Scholar
  65. 65.
    Imhof A, Woodward M, Doering A, Helbecque N, Loewel H, Amouyel P, et al. Overall alcohol intake, beer, wine, and systemic markers of inflammation in western Europe: results from three MONICA samples (Augsburg, Glasgow, Lille). Eur Heart J. 2004;25(23):2092–100.PubMedCrossRefGoogle Scholar
  66. 66.
    Fernandez-Real JM, Broch M, Vendrell J, Gutierrez C, Casamitjana R, Pugeat M, et al. Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes. 2000;49(3):517–20.PubMedCrossRefGoogle Scholar
  67. 67.
    Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004;53(3):693–700.PubMedCrossRefGoogle Scholar
  68. 68.
    Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB. Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr. 2005;81(4):780–6.PubMedGoogle Scholar
  69. 69.
    Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes. 2006;55(1):249–59.PubMedCrossRefGoogle Scholar
  70. 70.
    Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. Jama. 2004;291(14):1730–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56.PubMedCrossRefGoogle Scholar
  72. 72.
    Chandran M, Phillips SA, Ciaraldi T, Henry RR. Adiponectin: more than just another fat cell hormone? Diabetes Care. 2003;26(8):2442–50.PubMedCrossRefGoogle Scholar
  73. 73.
    Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003;148(3):293–300.PubMedCrossRefGoogle Scholar
  74. 74.
    Fu Y, Luo N, Klein RL, Garvey WT. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46(7):1369–79.PubMedCrossRefGoogle Scholar
  75. 75.••
    Lawlor DA, Nordestgaard BG, Benn M, Zuccolo L, Tybjaerg-Hansen A, Davey Smith G. Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study. Eur Heart J. 2013;34(32):2519–28. doi:10.1093/eurheartj/eht081eht081. This article provides novel evidence on potential causal associations between polymorphisms in alcohol metabolizing enzyme genes and various metabolic phenotypes.
  76. 76.•
    Kohsaka S, Jin Z, Rundek T, Homma S, Sacco RL, Di Tullio MR. Alcohol consumption and atherosclerotic burden in the proximal thoracic aorta. Atherosclerosis. 2011;219(2):794–8. doi:10.1016/j.atherosclerosis.2011.07.129S0021-9150(11)00759-3. This article provides unique evidence on potential genetic modification of the relationship between alcohol and subclinical atherosclerosis.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Bo P, Marchioni E, Bosone D, Soragna D, Albergati A, Micieli G, et al. Effects of moderate and high doses of alcohol on carotid atherogenesis. Eur Neurol. 2001;45(2):97–103.PubMedCrossRefGoogle Scholar
  78. 78.
    Fagrell B, De Faire U, Bondy S, Criqui M, Gaziano M, Gronbaek M, et al. The effects of light to moderate drinking on cardiovascular diseases. J Intern Med. 1999;246(4):331–40.PubMedCrossRefGoogle Scholar
  79. 79.
    Zureik M, Gariepy J, Courbon D, Dartigues JF, Ritchie K, Tzourio C, et al. Alcohol consumption and carotid artery structure in older French adults: the Three-City Study. Stroke. 2004;35(12):2770–5. doi:10.1161/01.STR.0000147968.48379.c3.PubMedCrossRefGoogle Scholar
  80. 80.
    Narita M, Kitagawa K, Nagai Y, Hougaku H, Hashimoto H, Sakaguchi M, et al. Effects of aldehyde dehydrogenase genotypes on carotid atherosclerosis. Ultrasound Med Biol. 2003;29(10):1415–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Hines LM, Hunter DJ, Stampfer MJ, Spiegelman D, Chu NF, Rifai N, et al. Alcohol consumption and high-density lipoprotein levels: the effect of ADH1C genotype, gender and menopausal status. Atherosclerosis. 2005;182(2):293–300. doi:10.1016/j.atherosclerosis.2005.02.005.PubMedCrossRefGoogle Scholar
  82. 82.
    Djousse L, Levy D, Herbert AG, Wilson PW, D'Agostino RB, Cupples LA, et al. Influence of alcohol dehydrogenase 1C polymorphism on the alcohol-cardiovascular disease association (from the Framingham Offspring Study). Am J Cardiol. 2005;96(2):227–32. doi:10.1016/j.amjcard.2005.03.050.PubMedCrossRefGoogle Scholar
  83. 83.
    Drogan D, Sheldrick AJ, Schutze M, Knuppel S, Andersohn F, di Giuseppe R, et al. Alcohol consumption, genetic variants in alcohol deydrogenases, and risk of cardiovascular diseases: a prospective study and meta-analysis. PLoS ONE. 2012;7(2):e32176. doi:10.1371/journal.pone.0032176PONE-D-11-18433.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Hoiseth G, Magnus P, Knudsen GP, Jansen MD, Naess O, Tambs K, et al. Is ADH1C genotype relevant for the cardioprotective effect of alcohol? Alcohol. 2013;47(2):81–4. doi:10.1016/j.alcohol.2012.12.005S0741-8329(12)00202-9.PubMedCrossRefGoogle Scholar
  85. 85.•
    Wang Y, Zhang Y, Zhang J, Tang X, Qian Y, Gao P, et al. Association of a functional single-nucleotide polymorphism in the ALDH2 gene with essential hypertension depends on drinking behavior in a Chinese Han population. J Hum Hypertens. 2013;27(3):181–6. doi:10.1038/jhh.2012.15jhh201215. Unlike most studies on ALDH2 and related genes, which are typically underpowered, this article provides evidence on genetic modification of the effects of alcohol in an adequately powered meta-analysis.PubMedCrossRefGoogle Scholar
  86. 86.
    Wang Q, Zhou S, Wang L, Lei M, Wang Y, Miao C, et al. ALDH2 rs671 Polymorphism and coronary heart disease risk among Asian populations: a meta-analysis and meta-regression. DNA Cell Biol. 2013;32(7):393–9. doi:10.1089/dna.2013.1995.PubMedCrossRefGoogle Scholar
  87. 87.
    Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74. doi:10.1056/NEJMoa1001282.
  88. 88.
    Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67. doi:10.1056/NEJMoa1107579.
  89. 89.
    Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care. 2005;28(3):719–25.PubMedCrossRefGoogle Scholar
  90. 90.
    Dakeishi M, Murata K, Sasaki M, Tamura A, Iwata T. Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers. Alcohol Alcohol. 2008;43(2):143–7. doi:10.1093/alcalc/agm173agm173.PubMedCrossRefGoogle Scholar
  91. 91.
    Yin G, Ohnaka K, Morita M, Tabata S, Tajima O, Kono S. Genetic polymorphisms of alcohol dehydrogenase and aldehyde dehydrogenase: alcohol use and type 2 diabetes in japanese men. Epidemiol Res Int. 2011;2011:8. doi:10.1155/2011/583682.CrossRefGoogle Scholar
  92. 92.
    Yokoyama A, Mizukami T, Matsui T, Yokoyama T, Kimura M, Matsushita S, et al. Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men. Alcohol Clin Exp Res. 2013;37(8):1391–401. doi:10.1111/acer.12108.PubMedCrossRefGoogle Scholar
  93. 93.
    Husemoen LL, Jorgensen T, Borch-Johnsen K, Hansen T, Pedersen O, Linneberg A. The association of alcohol and alcohol metabolizing gene variants with diabetes and coronary heart disease risk factors in a white population. PLoS ONE. 2010;5(8):e11735. doi:10.1371/journal.pone.0011735.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Beulens JW, Rimm EB, Hendriks HF, Hu FB, Manson JE, Hunter DJ, et al. Alcohol consumption and type 2 diabetes: influence of genetic variation in alcohol dehydrogenase. Diabetes. 2007;56(9):2388–94. doi:10.2337/db07-0181.PubMedCrossRefGoogle Scholar
  95. 95.
    Kavitha G, Damodara Reddy V, Paramahamsa M, Akhtar PM, Varadacharyulu NC. Role of nitric oxide in alcohol-induced changes in lipid profile of moderate and heavy alcoholics. Alcohol. 2008;42(1):47–53. doi:10.1016/j.alcohol.2007.10.006S0741-8329(07)00222-4.PubMedCrossRefGoogle Scholar
  96. 96.
    Hannuksela M, Marcel YL, Kesaniemi YA, Savolainen MJ. Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol. J Lipid Res. 1992;33(5):737–44.PubMedGoogle Scholar
  97. 97.
    Savolainen MJ, Hannuksela M, Seppanen S, Kervinen K, Kesaniemi YA. Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity. Eur J Clin Investig. 1990;20(6):593–9.CrossRefGoogle Scholar
  98. 98.
    Corella D, Saiz C, Guillen M, Portoles O, Mulet F, Gonzalez JI, et al. Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population. Atherosclerosis. 2000;152(2):367–76.PubMedCrossRefGoogle Scholar
  99. 99.
    Tanrikulu-Kucuk S, Ademoglu E, Gurdol F, Bilge AK, Mutlu-Turkoglu U, Nisanci Y. Cholesteryl ester transfer protein Taq1B polymorphism in an angiographically assessed Turkish population: no effects on coronary artery disease risk. Genet Test Mol Biomarkers. 2010;14(5):637–42. doi:10.1089/gtmb.2010.0069.PubMedCrossRefGoogle Scholar
  100. 100.
    Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. Jama. 2011;306(19):2099–109. doi:10.1001/jama.2011.1649306/19/2099.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • James N. Kiage
    • 1
  • Laurence O. James
    • 1
  • Edmond K. Kabagambe
    • 1
  1. 1.Division of Epidemiology, Department of MedicineVanderbilt University Medical CenterNashvilleUSA

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